title: Genomic alterations in human umbilical cord-derived mesenchymal stromal cells call for stringent quality control before any possible therapeutic approach.
abstract: OBJECTIVE
  The umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow-MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion.
  
  
  METHODS
  With the use of array-comparative genomic hybridization, we compared copy number variations of early (P2-P3) and late (>P5) passages of in vitro-expanded UC-MSCs.
  
  
  RESULTS
  In two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture.
  
  
  CONCLUSIONS
  Altogether, our results suggest that UC-MSC-based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.
authors.affiliation: Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico "San Matteo," Pavia, Italy; Laboratory of Neonatal Immunology, Fondazione IRCCS Policlinico "San Matteo," Pavia, Italy. Electronic address: alessandroborghesi@yahoo.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Borghesi
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Avanzini
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.forename: Melissa
authors.initials: M
authors.lastname: Mantelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Lenta
authors.forename: Valentina
authors.initials: V
authors.lastname: Achille
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Cerbo
authors.forename: Chryssoula
authors.initials: C
authors.lastname: Tzialla
authors.forename: Stefania
authors.initials: S
authors.lastname: Longo
authors.forename: Annalisa
authors.initials: A
authors.lastname: De Silvestri
authors.forename: Luc J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Paolo
authors.initials: P
authors.lastname: Manzoni
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Arsenio
authors.initials: A
authors.lastname: Spinillo
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D016922:Cellular Senescence; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D019942:Genes, p16; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D059785:Karyotype; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018895:Microsatellite Repeats / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology*
keywords: array comparative genomic hybridization; karyotype; mesenchymal stromal cells; umbilical cord